Project Summary/Abstract FMRI is an important tool to study neural circuitry in emotional aging. However, an important but under- studied issue in the interpretation of such fMRI data is that the BOLD signal used in fMRI is an indirect measure of neural activity and can be confounded by non-neural factors such as vascular function. Since vascular function is known to decline with age, it is important to re-examine the emotional aging fMRI literature (and the hypotheses generated from these findings) after accounting for vascular factors. The present proposal aims to conduct the first study in the field to characterize age-related differences in emotional neural circuit using advanced, vascular-corrected fMRI techniques. The PI has previously developed a novel technique to measure cerebrovascular reactivity (CVR) and cerebral blood volume (CBV) using gas-inhalation (e.g. CO2, O2) MRI, which can be used to calibrate the fMRI signal to improve its inference of neural activity. We have previously applied this technique in a memory- encoding aging study, and found that much of the previously reported decrease in visual activation in aging is due to vascular decline and that prefrontal hyperactivation in memory-encoding is more pervasive than previously thought. The proposed work sought to apply this exciting novel technique to the study of emotional aging. In the present study, we will examine how fMRI results in emotional aging are modified by vascular calibration by focusing on a well-established emotional circuit of neural interaction between amygdala and prefrontal cortex. In healthy younger and older subjects (N=30 each), we will perform task-evoked fMRI and resting-state fMRI. Gas-inhalation MRI will also be performed to measure vascular parameters of CVR and CBV. The central aim is to characterize age effect in emotional neural function after correcting for vascular differences, and consists of three sub-aims. Aim 1.1 will evaluate age-related differences in task-evoked neural activation after accounting for vascular factor. We will examine the age-related changes in amygdala and prefrontal fMRI responses as well as the correlation between them, with and without correction for CVR and CBV. Aim 1.2 will examine resting-state functional connectivity differences between younger and older participants after accounting for vascular factor, in particular the amygdala connectivity to other brain regions associated with emotional processing. Aim 1.3 will determine the association between fMRI signal and neurobehavioral assessment of emotion function in elderly subjects. We will also study the association between vascular parameters (CVR and CBV) and emotion ratings, to determine whether vascular health can affect emotion. The innovative methods developed in this proposal will lead to future applications to understand emotional circuitry in conditions that involve vascular pathology, including MCI and AD.